tbuckley/cabot-search huggingface dataset:
Association of Youth Suicides and County-Level Mental Health Professional Shortage Areas in the US
Authors: Jennifer A. Hoffmann, Megan M. Attridge, Michael S. Carroll, Norma-Jean E. Simon, Andrew F. Beck, Elizabeth R. Alpern
Journal: JAMA Pediatrics (2022)

Suicide is the second leading cause of death among US adolescents. Workforce shortages of mental health professionals in the US are widespread, but the association between mental health workforce shortages and youth suicides is not well understood.To assess the association between youth suicide rates and mental health professional workforce shortages at the county level, adjusting for county demographic and socioeconomic characteristics.This retrospective cross-sectional study included all US counties and used data of all US youlth suicides from January 2015, through December 31, 2016. Data were analyzed from July 1, 2021, through December 20, 2021.County health-professional shortage area designation for mental health, assigned by the US Health Resources and Services Administration based on mental health professionals relative to the population, level of need for mental health services, and service availability in contiguous areas. Designated shortage areas receive a score from 0 to 25, with higher scores indicating greater workforce shortages.Suicides by youth aged 5 to 19 years from 2015 to 2016 were identified from the US Centers for Disease Control and Prevention's Compressed Mortality File. A multivariable negative binomial regression model was used to analyze the association between youth suicide rates and mental health workforce shortage designation, adjusting for the presence of a children's mental health hospital and county-level markers of health insurance coverage, education, unemployment, income, poverty, urbanicity, racial and ethnic composition, and year. Similar models were performed for the subgroups of (1) firearm suicides and (2) counties assigned a numeric shortage score.During the study period, there were 5034 youth suicides (72.8% male and 68.2% non-Hispanic White) with an annual suicide rate of 3.99 per 100 000 youths. Of 3133 US counties, 2117 (67.6%) were designated as mental health workforce shortage areas. After adjusting for county characteristics, mental health workforce shortage designation was associated with an increased youth suicide rate (adjusted incidence rate ratio [aIRR], 1.16; 95% CI, 1.07-1.26) and an increased youth firearm suicide rate (aIRR, 1.27; 95% CI, 1.13-1.42). For counties with an assigned numeric workforce shortage score, the adjusted youth suicide rate increased 4% for every 1-point increase in the score (aIRR, 1.04; 95% CI, 1.02-1.06).In this cross-sectional study, US county mental health professional workforce shortages were associated with increased youth suicide rates. These findings may inform suicide prevention efforts.
Gene Expression and Autoantibody Analysis Revealing Distinct <scp>Ancestry‐Specific</scp> Profiles Associated With Response to Rituximab in Refractory Systemic Lupus Erythematosus
Authors: Lucy M. Carter, Adewonuola Alase, Zoe Wigston, Antonios Psarras, Agata Burska, Emily Sutton, Md Yuzaiful Md Yusof, John A. Reynolds, Neil McHugh, Paul Emery, Miriam Wittmann, Ian N. Bruce, Edward M. Vital
Journal: Arthritis & Rheumatology (2022)

Objective Gene expression profiles are associated with the clinical heterogeneity of systemic lupus erythematosus (SLE) but are not well studied as biomarkers for therapy. We studied gene expression and response to rituximab in a multiethnic UK cohort who were refractory to standard therapy. Methods We evaluated baseline expression levels of transcripts known to associate with clinical features of SLE using a 96‐probe TaqMan array and whole blood samples from 213 patients with active SLE who had been prospectively enrolled in the British Isles Lupus Assessment Group (BILAG) Biologics Register. We measured autoantibodies using immunoprecipitation and enzyme‐linked immunosorbent assays. We determined responses to first‐cycle rituximab at 6 months from treatment start in 110 SLE patients by assessing BILAG 2004 disease activity. Results Interferon gene expression scores were lower in patients of European ancestry than in all other ancestry groups. The relationship between blood interferon gene expression scores and scores annotated to plasmablasts, neutrophils, myeloid lineage, inflammation, and erythropoiesis differed between patients of European and non‐European ancestries. Hierarchical clustering revealed 3 distinct non‐European ancestry patient subsets with stratified responses to rituximab that were not explained by sociodemographic and clinical variables, with responses lowest in an interferon‐low, neutrophil‐high cluster and highest in a cluster with high expression levels across all signatures ( P &lt; 0.001). Clusters in European ancestry patients did not predict response to rituximab but segregated patients by global disease activity and renal involvement. In both ancestral groups, interferon‐high clusters were associated with U1 RNP/Sm antibodies. Conclusion Ancestry appears central to the immunologic and clinical heterogeneity in SLE. These results suggest that ancestry, disease activity, and transcriptional signatures could each assist in predicting the effectiveness of B cell depletion therapies. image
Surgeon-anatomist to robotic technician? The evolving role of the surgeon over three centuries
Authors: Sean Patrick Hughes, Iain Macintyre
Journal: Journal of the Royal Society of Medicine (2022)

In the 18th century, anatomy was the principal science underlying surgical practice. Over the next three centuries, the scientific basis of surgery changed dramatically. Morbid anatomy led to the understanding of organ-based pathologies that allowed surgeons to remove, reconstruct and in some cases replace internal organs. In the 19th century, the new science of microbiology facilitated antisepsis, then asepsis as surgery progressed from a craft to a scientific discipline. Yet many surgeons believed that surgery was not merely a science but also an art, in which the creativity of the doctor was necessary for progress. Surgical advancement depended on creative individuals with innovative flair, prepared to pioneer often risky procedures in the face of mainstream opposition. The 20th century saw a series of changes that made such individualism more difficult. 'Scientific Management' when applied to surgery decreed that procedures be performed according to predetermined schedules, a drive to uniformity producing better outcomes and diminishing individual variation. Yet inventive individuals continued to produce surgical advances. In the 21st century, moves toward standardisation developed further. The escalating safety culture in surgery moderates the introduction of novel, potentially riskier procedures, while more and more regulation increasingly requires surgeons to adhere to guidelines and protocols, further restricting surgical individualism. Moreover, the role of the individual is further diminished, as surgical care is delivered by teams, both in deciding management in major cases and in the operating theatre. The introduction of robotics into surgery has led to the suggestion that the role of the surgeon may become that of a technician. Will these constraints, and greater patient involvement in decisions, allow tomorrow's surgeons the freedom to innovate? We believe that the pioneering spirit, imagination and flair will not be lost. Tomorrow's surgeons must remain doctors, showing the compassion and empathy that robots cannot provide.
Why frightening imaginary worlds? Morbid curiosity and the learning potential of horror
Authors: Coltan Scrivner, Mathias Clasen
Journal: Behavioral and Brain Sciences (2022)

Abstract In addition to satisfying a predisposition for exploration, fiction with imaginary worlds may also appeal to morbid curiosity, an adaptive motivation to seek out information about dangerous situations. Most imaginary worlds contain narrative elements of danger, and immersion in such worlds may provide people with information that would be costly to acquire in the real world.
Imaginary worlds pervade forager oral tradition
Authors: Michelle Scalise Sugiyama
Journal: Behavioral and Brain Sciences (2022)

Abstract Imaginary worlds recur across hunter-gatherer narrative, suggesting that they are an ancient part of human life: to understand their popularity, we must examine their origins. Hunter-gatherer fictional narratives use various devices to encode factual information. Thus, participation in these invented worlds, born of our evolved ability to engage in pretense, may provide adaptations with information inputs that scaffold their development.
Unusual Extramedullary Manifestation in Multiple Myeloma
Authors: Dimitrios Strauss, Christos Sachpekidis, Ulrike Dapunt, Hartmut Goldschmidt, Antonia Dimitrakopoulou-Strauss
Journal: Clinical Nuclear Medicine (2022)

Abstract A 73-year-old man with multiple myeloma (initial diagnosis 21 months earlier) was referred to our center for a whole-body 18 F-FDG PET/CT. We detected a bilateral synchronous testicular manifestation, which was confirmed by histopathology after orchiectomy. Besides hypermetabolic lesions in the spine and ribs (most likely old fractures), known osteolysis showed no uptake. Extramedullary manifestation occurs in 13% to 20% of cases, among these 4% demonstrate testicular manifestation, which is associated with poor survival rates. Optimal therapy management is still unclear, due to limited data. To the authors’ knowledge, so far only 3 comparable cases have been described.
Cognitive exploration drives engagement and re-engagement with imaginary worlds, but not spatial exploration as predicted by evolutionary theory
Authors: Rebecca Dunk, Raymond A. Mar
Journal: Behavioral and Brain Sciences (2022)

Abstract The empirical evidence for exploration underlying the appeal of imaginary worlds is mostly absent or contradictory. Openness, and the cognitive exploration it represents, provides a better account than the overall drive to explore predicted by evolutionary theory. Furthermore, exploration cannot explain why imaginary worlds foster frequent re-engagement.
Incidence and clinical correlates of <i>de‐novo</i> aortic regurgitation with a fully magnetically levitated left ventricular assist device: a <scp>MOMENTUM 3</scp> trial portfolio analysis
Authors: Nir Uriel, Carmelo Milano, Richa Agarwal, Sangjin Lee, Joseph Cleveland, Daniel Goldstein, AiJia Wang, Daniel Crandall, Mandeep R. Mehra
Journal: European Journal of Heart Failure (2022)
TREM2 and microglia exosomes: a potential highway for pathological tau
Authors: Nimansha Jain, Jason D. Ulrich
Journal: Molecular Neurodegeneration (2022)

Abstract Tau pathology appears to spread along neuronal networks via the template misfolding of tau by pathological tau conformations. The mechanisms underlying neuron-to-neuron transmission of tau are unclear and recent work demonstrates a role for microglia in the spread of tau pathology. In this Commentary, we discuss a recent study that found that loss of TREM2 expression resulted in exacerbated spread of tau pathology that depended on microglial exosomes. These important findings highlight the role of the microglial endolysosomal system and TREM2 in the spread of tau pathology.
Improving the circulation time and renal therapeutic potency of extracellular vesicles using an endogenous ligand binding strategy
Authors: Shuyun Liu, Ke Lv, Yizhuo Wang, Peng Lou, Pingya Zhou, Chengshi Wang, Lan Li, Guangneng Liao, Yong Zhang, Younan Chen, Jingqiu Cheng, Yanrong Lu, Jingping Liu
Journal: Journal of Controlled Release (2022)
Cerium oxide nanoparticles with antioxidative neurorestoration for ischemic stroke
Authors: Xiang Li, Zhihui Han, Tianyi Wang, Cheng Ma, Haiying Li, Huali Lei, Yuqi Yang, Yuanjie Wang, Zifan Pei, Zhuang Liu, Liang Cheng, Gang Chen
Journal: Biomaterials (2022)
Substrate Affinity Versus Catalytic Efficiency: Ancestral Sequence Reconstruction of tRNA Nucleotidyltransferases Solves an Enzyme Puzzle
Authors: Martina Hager, Marie-Theres Pöhler, Franziska Reinhardt, Karolin Wellner, Jessica Hübner, Heike Betat, Sonja Prohaska, Mario Mörl
Journal: Molecular Biology and Evolution (2022)

Abstract In tRNA maturation, CCA-addition by tRNA nucleotidyltransferase is a unique and highly accurate reaction. While the mechanism of nucleotide selection and polymerization is well understood, it remains a mystery why bacterial and eukaryotic enzymes exhibit an unexpected and surprisingly low tRNA substrate affinity while they efficiently catalyze the CCA-addition. To get insights into the evolution of this high-fidelity RNA synthesis, the reconstruction and characterization of ancestral enzymes is a versatile tool. Here, we investigate a reconstructed candidate of a 2 billion years old CCA-adding enzyme from Gammaproteobacteria and compare it to the corresponding modern enzyme of Escherichia coli. We show that the ancestral candidate catalyzes an error-free CCA-addition, but has a much higher tRNA affinity compared with the extant enzyme. The consequence of this increased substrate binding is an enhanced reverse reaction, where the enzyme removes the CCA end from the mature tRNA. As a result, the ancestral candidate exhibits a lower catalytic efficiency in vitro as well as in vivo. Furthermore, the efficient tRNA interaction leads to a processive polymerization, while the extant enzyme catalyzes nucleotide addition in a distributive way. Thus, the modern enzymes increased their polymerization efficiency by lowering the binding affinity to tRNA, so that CCA synthesis is efficiently promoted due to a reduced reverse reaction. Hence, the puzzling and at a first glance contradicting and detrimental weak substrate interaction represents a distinct activity enhancement in the evolution of CCA-adding enzymes.
The deep history of imaginary worlds
Authors: Polly Wiessner
Journal: Behavioral and Brain Sciences (2022)

Abstract If recent exploratory traditions tap into evolved psychological dispositions to explore, wouldn't humans be expected to have drawn on such dispositions long before the written word? Trickster oral traditions fill this role in all levels of society, affluence, and on all continents, inverting the boundaries of social worlds and those between humans and animals, fostering cultural innovation.
Optimal Timing of Anterior Cruciate Ligament Reconstruction in Patients With Anterior Cruciate Ligament Tear
Authors: Xianyue Shen, Tong Liu, Shenghao Xu, Bo Chen, Xiongfeng Tang, Jianlin Xiao, Yanguo Qin
Journal: JAMA Network Open (2022)

The timing of surgery has been regarded as a key factor in anterior cruciate ligament reconstruction (ACLR), and early vs delayed ACLR remains a controversial topic.To synthesize up-to-date published data from randomized clinical trials (RCTs) comparing early vs elective delayed ACLR for patients with ACL deficiency, in terms of clinical outcomes and complications.The PubMed, Cochrane Library, and Web of Science databases were systematically searched until September 9, 2022.All published RCTs comparing clinical and functional outcomes and complications associated with early ACLR vs elective delayed ACLR.Two reviewers independently extracted relevant data and assessed the methodological quality following the PRISMA guidelines.Due to the clinical heterogeneity, the random-effects model was preferred. The primary outcomes were functional outcomes and complications. The Mantel-Haenszel test was used to evaluate dichotomous variables and the inverse variance method was used to assess continuous variables.This meta-analysis included 972 participants in 11 RCTs stratified by follow-up duration. The following factors did not differ between early and delayed ACLR: operative time (mean difference, 4.97; 95% CI, -0.68 to 10.61; P = .08), retear (OR, 1.52; 95% CI, 0.52-4.43; P = .44), and infection (OR, 3.80; 95% CI, 0.77-18.79; P = .10). There were also no differences between groups in range of motion, knee laxity, International Knee Documentation Committee (IKDC rating scale), and Tegner score. IKDC score (mean difference, 2.77; 95% CI, 1.89-3.66; P < .001), and Lysholm score at 2-year follow-up (mean difference, 2.61; 95% CI, 0.74-4.48; P = .006) significantly differed between early and delayed ACLR. In addition, the timing of surgery was redefined in the included RCTs and subgroup analyses were performed, which validated the robustness of the principal results.This systematic review and meta-analysis found that early ACLR was not superior to delayed ACLR in terms of most factors analyzed, except for IKDC and Lysholm scores. This information should be available to patients with ACL deficiency and clinicians as part of the shared decision-making process of treatment selection.
Middle-earth wasn't built in a day: How do we explain the costs of creating a world?
Authors: Aaron D. Lightner, Cynthiann Heckelsmiller, Edward H. Hagen
Journal: Behavioral and Brain Sciences (2022)

Abstract Dubourg and Baumard explain why fictional worlds are attractive to consumers. A complete account of fictional worlds, however, should also explain why some people create them. Creation is a costly and time-consuming process that does not resemble exploration but does resemble the culturally universal phenomenon of knowledge specialization.
Using imaginary worlds for real social benefits
Authors: Shira Gabriel, Melanie C. Green, Esha Naidu, Elaine Paravati
Journal: Behavioral and Brain Sciences (2022)

Abstract We argue that imaginary worlds gain much of their appeal because they fulfill the fundamental need of human beings to feel connected to other humans. Immersion into story worlds provides a sense of social connection to the characters and groups represented in the world. By fulfilling the need to belong, imaginary worlds provide a buffer against rejection and loneliness.
Angiotensin receptor blockers for the treatment of covid-19: pragmatic, adaptive, multicentre, phase 3, randomised controlled trial
Authors: Meg J Jardine, Sradha S Kotwal, Abhinav Bassi, Carinna Hockham, Mark Jones, Arlen Wilcox, Carol Pollock, Louise M Burrell, James McGree, Vinay Rathore, Christine R Jenkins, Lalit Gupta, Angus Ritchie, Ashpak Bangi, Sanjay D’Cruz, Andrew J McLachlan, Simon Finfer, Michelle M Cummins, Thomas Snelling, Vivekanand Jha
Journal: BMJ (2022)

Abstract Objective To determine whether disrupting the renin angiotensin system with angiotensin receptor blockers will improve clinical outcomes in people with covid-19. Design CLARITY was a pragmatic, adaptive, multicentre, phase 3, randomised controlled trial. Setting 17 hospital sites in India and Australia. Participants Participants were at least 18 years old, previously untreated with angiotensin receptor blockers, with a laboratory confirmed diagnosis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection who had been admitted to hospital for management of covid-19. Intervention Oral angiotensin receptor blockers (telmisartan in India) or placebo (1:1) for 28 days. Main outcome measures The primary endpoint was covid-19 disease severity using a modified World Health Organization Clinical Progression Scale (WHO scale) at day 14. Secondary outcomes were WHO scale scores at day 28, mortality, intensive care unit admission, and respiratory failure. Analyses were evaluated on an ordinal scale in the intention-to-treat population. Results Between 3 May 2020 and 13 November 2021, 2930 people were screened for eligibility, with 393 randomly assigned to angiotensin receptor blockers (of which 388 (98.7%) to telmisartan 40 mg/day) and 394 to the control group. 787 participants were randomised: 778 (98.9%) from India and nine (1.1%) from Australia. The median WHO scale score at day 14 was 1 (interquartile range 1-1) in 384 participants assigned angiotensin receptor blockers and 1 (1-1) in 382 participants assigned placebo (adjusted odds ratio 1.51 (95% credible interval 1.02 to 2.23), probability of an odds ratio of &gt;1 (Pr(OR&gt;1)=0.98). WHO scale scores at day 28 showed little evidence of difference between groups (1.02 (0.55 to 1.87), Pr(OR&gt;1)=0.53). The trial was stopped when a prespecified futility rule was met. Conclusions In patients admitted to hospital for covid-19, mostly with mild disease, not requiring oxygen, no evidence of benefit, based on disease severity score, was found for treatment with angiotensin receptor blockers, using predominantly 40 mg/day of telmisartan. Trial registration ClinicalTrials.gov NCT04394117 .
Is it time to consider allergen immunotherapy earlier in the management of allergic asthma?
Authors: Graham Roberts
Journal: European Respiratory Journal (2022)

Despite modern pharmacotherapy, many patients continue to experience ongoing symptoms and exacerbations of their asthma. Allergen immunotherapy is used to manage asthma in some countries but not others. Is it time to utilise allergen immunotherapy more generally in the management of asthma? Allergen immunotherapy should be considered as an add-on therapy earlier in the management of allergic asthma https://bit.ly/3SiPbaY
Going after CD70 with CAR T, NK Cells
Journal: Cancer Discovery (2022)

CD70 has emerged as a promising solid tumor target for chimeric antigen receptor (CAR)-bearing T or natural killer (NK) cells, with one allogeneic CAR T-cell therapy, CTX130, showing preliminary efficacy in renal cell carcinoma. Further, assessments of a cord blood-derived CAR-NK alternative have started; the trial will be the first to use cryopreserved NK cells.
The development of the imagination and imaginary worlds
Authors: Sarah R. Beck, Paul L. Harris
Journal: Behavioral and Brain Sciences (2022)

Abstract Evidence from developmental psychology on children's imagination is currently too limited to support Dubourg and Baumard's proposal and, in several respects, it is inconsistent with their proposal. Although children have impressive imaginative powers, we highlight the complexity of the developmental trajectory as well as the close connections between children's imagination and reality.
Health Care Access on the Line — Audio-Only Visits and Digitally Inclusive Care
Authors: Helen K. Hughes, Brian W. Hasselfeld, Jeremy A. Greene
Journal: New England Journal of Medicine (2022)

Interview with Dr. Ateev Mehrotra on federal pandemic-era telemedicine policies and research that could help inform permanent regulations. (09:48)Download Action is needed to ensure that the digital health revolution helps bring about a more equitable care delivery system. Audio-only visits could be a stepping stone to digitally inclusive health care.
Imaginary worlds are attractive because they simulate multiple adaptive problems and encode real-world information
Authors: Lawrence Sugiyama
Journal: Behavioral and Brain Sciences (2022)

Abstract Organisms don't explore for exploration's sake: exploratory psychology is regulated by inputs from multiple adaptations dedicated to processing information from different domains of ancestral adaptive relevance. As holistic representations of environments, imaginary worlds simulate multiple adaptive problems, solutions, and outcomes, thereby engaging numerous emotional systems and providing potentially useful information. Their popularity is thus best understood in terms of the full spectrum of information domains they comprise.
Effect of Vitamin C Supplementation for Pregnant Smokers on Offspring Airway Function and Wheeze at Age 5 Years
Authors: Cindy T. McEvoy, Lyndsey E. Shorey-Kendrick, Kristin Milner, Julia Harris, Brittany Vuylsteke, Michelle Cunningham, Christina Tiller, Jaclene Stewart, Diane Schilling, Julie Brownsberger, Hope Titus, Kelvin D. MacDonald, David Gonzales, Annette Vu, Byung S. Park, Eliot R. Spindel, Cynthia D. Morris, Robert S. Tepper
Journal: JAMA Pediatrics (2022)

Vitamin C supplementation (500 mg/d) for pregnant smokers has been reported to increase offspring airway function as measured by forced expiratory flow (FEF) through age 12 months; however, its effects on airway function at age 5 years remain to be assessed.